Neonatal mortality is an important global public health challenge. Although advances in neonatal intensive care have led to improved survival of premature infants, sepsis continues to be an important cause of morbidity and mortality worldwide. Exposure of the preterm brain to inflammatory mediators during infectious episodes contributes to brain injury and poor developmental outcome. It has been demonstrated that breast milk has a beneficial effect on neurodevelopment outcomes in preterm infants. We hypothesize that lactoferrin, an iron binding protein present in mammalian milk, is the major factor responsible for this effect due to its antimicrobial and immunomodulatory properties. We have found that lactoferrin not only inhibits growth;it impairs virulence of some of the major pathogens by decreasing their ability to adhere to or to invade mammalian cells, and by binding to, or degrading, specific virulence proteins. Lactoferrin may protect infants from sepsis by blocking attachment and invasion of organisms in the gut. We propose a clinical trial in premature infants to determine the effect of lactoferrin on occurrence of sepsis and to determine whether as a result of decreased infections, infants grow and develop better after having been on lactoferrin. Specific aim 1: We will test the hypothesis that oral bovine lactoferrin supplementation prevents serious infections in preterm infants. We will conduct a randomized placebo-controlled double blind study in premature infants <2000 gm in Neonatal Units in Lima, Peru to determine whether bovine lactoferrin prevents the first episode of late-onset sepsis. Specific aim 2: We will test the hypothesis that bovine lactoferrin supplementation promotes better neurodevelopment and growth outcomes in preterm infants assessed by the Mullen Scales of Early Learning, a standardized neurologic exam and growth measurements at 18 and 24 months corrected age. The use of lactoferrin as a broad-spectrum non-pathogen specific antimicrobial protective protein is an innovative approach. If successful, this study could profoundly affect clinical care of neonates both in the developed and developing world.